Pharmacokinetic principles for the central nervous system were established by demonstrating in rats that cerebrovascular permability of nonelectrolyte and organic electrolyetes is related linearly to the octanol/water partition coefficient. Drug entry into the brain now can be predicted from the partition coefficient and plasma concentration. Permeability to 14C-sucrose is very low and unaffected by senescence in the rat. This suggests, contrary to the immune hypothesis for brain aging, that the blood-brain barrier at the cerebral vasculature is not disrupted in the aged brain. Barrier permeability can be reversibly increased by infusing a hypertonic solution of arabinose into the carotid artery of rats. Tight junctions between cerebrovascular endothelial cells widen to intravascular substances. The osmotic method to open the blood-brain barrier transiently elevates brain water and regional brain glucose consumption, but does not produce long-term pathology. It has been used as a pharmacological tool in animals to allow protein antibodies and enzymes into the brain, as well as amines which modify cerebral blood flow.